Ocriplasmin 375micrograms/0.3ml solution for injection vials

BACKGROUND: We conducted a systematic review to compare the effects of pneumatic vitreolysis (PV), enzymatic vitreolysis (EVL) with ocriplasmin, and pars plana vitrectomy (PPV) on vitreomacular traction (VMT) syndrome and macular holes (MHs) to assess their efficacy as treatment options. METHODS: Databases, including PubMed, ClinicalTrials.gov ( www. CLINICALTRIALS: gov ), the Cochrane Central Register of Controlled Trials (CENTRAL)-including the Cochrane Eyes and Vision Group Trials Register (The Cochrane Library 2013, Issue 2)-, Ovid MEDLINE, and EMBASE (January 2000-October 2022), were searched to identify studies comparing the outcomes of PV versus PPV, PPV versus ocriplasmin and ocriplasmin versus PV. RevMan 5.1 was used for the meta-analysis of the studies. RESULTS: Among the 89 studies, 79 were considered eligible for qualitative analysis, and 10 quantitative studies were subjected to meta-analysis. PPV resulted in better postoperative visual acuity improvement than ocriplasmin (standardized mean deviation (SMD) = 0.38, 95% CI 0.03-0.73, p = 0.0003). PV resulted in no significant difference in visual improvement compared with PPV (SMD = - 0.15, 95% CI - 0.47 to 0.16, p = 0.35). PPV was significantly more effective in terms of the VMT release rate (risk ratio = 0.48, 95% CI 0.38-0.62, p = 0.00001) and MH closure rate (risk ratio = 0.49, 95% CI 0.30-0.81, p = 0.006) than ocriplasmin. PV was more effective than ocriplasmin in terms of the VMT release rate (risk ratio = 0.49, 95% CI 0.35-0.70, p = 0.0001). Qualitative analysis showed MH closure rates of 46%, 47.8%, and 95% and VMT releases rates of 46%, 68% and 100% after ocriplasmin, PV, and PPV treatments, respectively. Adverse events and postoperative complications occurring after treatment have also been documented in these studies. CONCLUSION: PPV appears to be the most promising option for MH closure and VMT release, with fewer serious complications than EVL or PV. However, given the limited number of studies comparing these treatments, further research is needed to establish the superiority of PPV over the other options.

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Symptomatic vitreomacular adhesion (sVMA) impedes visual acuity and quality. Ocriplasmin is a recombinant protease, which may be injected into the vitreous cavity to treat this condition, yet controversy remains with respect to its effectiveness and safety, particularly its patient selection standard. In this systematic review, the PubMed, Embase, and the Cochrane Library were searched to identify studies published prior to August 2020 on the impact of ocriplasmin treatment on VMA release, macular hole (MH) closure, and/or related adverse events (AEs). Data were pooled using a random-effects model. Risk ratios (RRs) with 95% CIs were calculated. Of 1,186 articles reviewed, 5 randomized controlled trials and 50 cohort studies were ultimately included, representing 4,159 patients. Ocriplasmin significantly increased the rate of VMA release (RR, 3.61; 95% CI, 1.99-6.53; 28 days after treatment) and MH closure (RR, 3.84; 95% CI, 1.62-9.08; 28 days after treatment) and was associated with visual function improvement. No increased risk for overall AEs was seen in ocriplasmin treatment. The proportion of VMA release and MH closure in patients was 0.50 and 0.36, respectively. VMA release was more likely in patients with absence of epiretinal membrane (ERM). Patients with smaller MH diameter were more likely to achieve MH closure. Evidence from included studies suggests that ocriplasmin is a suitable and safe approach for treating sVMA. ERM and MH status are important factors when considering ocriplasmin treatment.

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PURPOSE: Effectiveness of ocriplasmin for vitreomacular traction (VMT) varies depending on the presence of common ocular conditions and patient selection criteria. We carried out a systematic literature review and meta-analysis of ocriplasmin studies conducted in real-world settings (RWS) and compared outcomes with those from randomized controlled trials (RCTs). METHODS: We included prospective and retrospective studies from RWS documenting effectiveness of ocriplasmin in patients with VMT with or without MH, and RCTs of ocriplasmin versus control. Key end-points were vitreomacular adhesion resolution (VMAR), nonsurgical MH closure, need for vitrectomy and safety. We conducted meta-regression on pooled results to evaluate effects of baseline covariates and study design on outcomes. RESULTS: Thirty RWS (2402 patients) and 5 RCTs (737 patients) were included epiretinal membrane (ERM) and broad VMA were more prevalent in RCTs. Primary VMAR, vitrectomy and MH closure rates were comparable between RWS and RCTs. Rates of nsVMAR were significantly higher in RWS than RCTs (odds ratio 1.66; 95% confidence interval [CI]: 1.18-2.34). nsVMAR rates were inversely associated with ERM prevalence (odds ratio 0.20; 95% CI: 0.08-0.51). Compared with the recent OASIS trial, RWS reported a higher incidence of new/worsening subretinal fluid cases and less photophobia, photopsia, vitreous floaters, electroretinogram abnormalities and MH progression. CONCLUSIONS: Ocriplasmin was significantly more effective in achieving nsVMAR in RWS than in RCTs. Lower ERM prevalence in RWS was the single significant explanatory variable for this difference. Conclusions on ocriplasmin safety in RWS are limited due to inconsistent reporting.

Abstract licence: CC BY-NC-ND

BACKGROUND: The purpose of this study was using bioinformatics tools to identify biomarkers and molecular factors involved in the diagnosis of colorectal cancer, which are effective for the diagnosis and treatment of the disease. METHODS: We determined differentially expressed genes (DEGs) related to colorectal cancer (CRC) using the data series retrieved from GEO database. Then the weighted gene co-expression network analysis (WGCNA) was conducted to explore co-expression modules related to CRC diagnosis. Next, the relationship between the integrated modules with clinical features such as the stage of CRC was evaluated. Other downstream analyses were performed on selected module genes. RESULTS: In this study, after performing the WGCNA method, a module named blue module which was more significantly associated with the CRC stage was selected for further evaluation. Afterward, the Protein-protein interaction network through sting software for 154 genes of the blue module was constructed and eight hub genes were identified through the evaluation of constructed network with Cytoscape. Among these eight hub genes, upregulation of MMP9, SERPINH1, COL1A2, COL5A2, COL1A1, SPARC, and COL5A1 in CRC was validated in other microarray and TCGA data. Based on the results of the mRNA-miRNA interaction network, SERPINH1 was found as a target gene of miR-940. Finally, results of the DGIDB database indicated that Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, and Bevacizumab, could be used as a therapeutic agent for targeting the MMP9. Furthermore, Ocriplasmin and Collagenase clostridium histolyticum could target COL1A1, COL1A2, COL5A1, and COL5A2. CONCLUSION: Taken together, the results of the current study indicated that seven hub genes including COL1A2, COL5A1, COL5A2, SERPINH1, MMP9, SPARC, and COL1A1 which were upregulated in CRC could be used as a diagnostic and progression biomarker of CRC. On the other hand, miR-940 which targets SERPINH1 could be used as a potential biomarker of CRC. More ever, Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, Bevacizumab, Ocriplasmin , and Collagenase clostridium histolyticum were introduced as therapeutic agents for CRC which their therapeutic potential should be evaluated experimentally.

Abstract licence: CC BY-NC-ND

BACKGROUND: Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers. METHODS: Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR. RESULTS: We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD. CONCLUSION: COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.

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Background: Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, and an overall understanding of the molecular mechanisms related to IDD is still lacking. The purpose of this study was to explore gene signatures and immune cell infiltration related to IDD via bioinformatics analysis. Methods: A total of five expression profiles of mRNA and non-coding RNA were downloaded from the Gene Expression Omnibus (GEO) database. The potentially involved lncRNA/circRNA–miRNA–mRNA networks and protein-protein interaction networks were constructed by miRNet, circBank, STRING, and the Cytoscape database. Gene ontology, Kyoto Encyclopaedia of Genes and Genomes Analysis, Gene Set Enrichment Analysis, Gene Set Variation Analysis, Immune Infiltration Analysis, and Drug-Gene Interaction were used to analyse the top 20 hub genes. RT-qPCR was conducted to confirm the 12 differential expressions of genes both in the nucleus pulposus and annulus fibrosus tissues Results: There were 346 differentially expressed mRNAs, 12 differentially expressed miRNAs, 883 differentially expressed lncRNAs, and 916 differentially expressed circRNAs in the GEO database. Functional and enrichment analyses revealed hub genes associated with platelet activation, immune responses, focal adhesion, and PI3K-Akt signalling. The apoptotic pathway, the reactive oxygen species pathway, and oxidative phosphorylation play an essential role in IDD. Immune infiltration analysis demonstrated that the Treg cells had significant infiltration, and three levels of immune cells, including dendritic cells, Th2 cells, and tumour-infiltrating lymphocytes, were inhibited in IDD. Drug-gene interaction analysis showed that COL1A1 and COL1A2 were targeted by collagenase clostridium histolyticum, ocriplasmin, and PDGFRA was targeted by 66 drugs or molecular compounds. Finally, 24 cases of IDD tissues and 12 cases of normal disc tissues were collected, and the results of RT-qPCR were consistent with the bioinformatics results. Conclusion: Our data indicated that the 20 hub genes and immune cell infiltration were involved in the pathological process of IDD. In addition, the PDGFRA and two potential drugs were found to be significant in IDD development.

Abstract licence: CC BY